2025-26 Project (Teh & Reljic)

Developing Human Papillomavirus (HPV) Vaccines in Stable Nicotiana tabacum: Advancing Plant-Based Solutions for Accessible Immunization

SUPERVISORY TEAM

Supervisor

Dr Audrey Teh at City St George’s
Email: ateh@sgul.ac.uk

Co-Supervisor

Professor Rajko Reljic at City St George’s
Email: rreljic@sgul.ac.uk

PROJECT SUMMARY

Project Summary

Plant-Powered Vaccines: Harnessing tobacco to develop affordable Human Papillomavirus (HPV) vaccines   

Join a cutting-edge research project focused on producing affordable HPV vaccines through plant molecular farming, using stable Nicotiana tabacum plants. This exciting PhD opportunity aims to overcome the high costs of current HPV vaccines by pioneering the first-ever production of HPV virus-like particles (VLPs) in stable plants. This novel approach offers a sustainable, cost-effective solution for vaccine production, particularly suited to low- and middle-income countries (LMICs).   

The project involves a range of advanced techniques, including gene design, plant transformation, purification optimization, and preclinical evaluation. You will work in collaboration with leading international labs, contributing to global health by improving vaccine accessibility in resource-limited settings.   

We are looking for passionate, high-quality candidates with backgrounds in molecular biology, biotechnology, or related fields, eager to tackle one of the most pressing challenges in vaccine development.

Project Key Words

Plant Molecular Farming, HPV Vaccine

MRC LID Themes

  1. Infectious Disease
  2. Global Health
  3. Translational and Implementation Research

Skills

MRC Core Skills

  1. Interdisciplinary skills
  2. Whole organism physiology
  3. Quantitative skills

Skills we expect a student to develop/acquire whilst pursuing this project

• Molecular biology, DNA manipulation
• Agrobacterium transformation and tissue culture of plant and animal cells
• Protein purification and affinity chromatography
• Optimization of downstream purification
• Immunological, biochemical and optical techniques
• In vitro cell-based assays; flow cytometry
• In vivo studies

Routes

Which route/s are available with this project?

  • 1+4 = Yes
  • +4 = Yes

Possible Master’s programme options identified by supervisory team for 1+4 applicants:

  • City St George’s – MRes Biomedical Science – Infection and Immunity

Full-time/Part-time Study

Is this project available for full-time study? Yes
Is this project available for part-time study? No

Location & Travel

Students funded through MRC LID are expected to work on site at their primary institution, meeting – at the minimum – the institutional research degree regulations and expectations. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training (for research degree study). Other travel expectations and opportunities highlighted by the supervisory team are noted below.

Primary location for duration of this research degree: City St George’s, London

Travel requirements for this project: Travel to the University of Leicester for in vivo studies.

Eligibility/Requirements

Particular prior educational requirements for a student undertaking this project

  • Minimum City St George’s institutional eligibility criteria for doctoral study.
  • Good BSc degree and/or MRes/MSci in appropriate subject area

Other useful information

  • Potential Industrial CASE (iCASE) conversion? = No

PROJECT IN MORE DETAIL

Scientific description of this research project

BACKGROUND & SIGNIFICANCE 
HPV remains a major cause of cervical cancer globally, with LMICs disproportionately affected due to limited vaccine access. Current vaccines are costly, primarily due to complex production in mammalian cells. This project aims to produce HPV virus-like particles (VLPs) in stable Nicotiana tabacum plants, a first, building on previous success from other groups with transient plant expression systems. Stable expression offers better transferability to LMICs, requiring less infrastructure and investment, making it more sustainable and cost-effective for localized vaccine production. By lowering production costs, this project aims to improve vaccine accessibility in resource-limited settings.

PROJECT OBJECTIVES 
The primary objective of this project is to develop genetically stable plants capable of expressing the Human Papillomavirus (HPV) L1 protein under inducible conditions, optimizing expression and purification processes to ensure the system’s sustainability for LMICs.    

The secondary objective is to evaluate the immunogenicity and efficacy of the plant-derived HPV vaccine in preclinical models, with a view to scaling up production and distribution in LMICs.

TECHNIQUES USED
1. Gene Construct Design and Cloning: This involves the design and assembly of gene constructs containing the HPV L1 proteins of two HPV types (35 and 52) that are relevant to LMICs, followed by the generation of stable transgenic plants.  Light-inducible and copper sulphate (CuSO4)-inducible promoter systems will be tested to overcome gene silencing issues in stable expression systems.
2. Plant Transformation: Stable transformation of Nicotiana tabacum using Agrobacterium-mediated methods.
3. Characterization of Virus-Like Particles (VLPs): Structural characterization will be performed using Western blot analysis and transmission electron microscopy (TEM)
4. Preclinical Evaluation: The immunogenicity and efficacy of the plant-derived vaccine will be assessed using animal models, analysing immune responses in sera through ELISA and pseudovirion-based neutralization assays (PBNAs).   

AVAILABILITY OF SPECIALIST MATERIALS 
Specialist materials required for the project, including Nicotiana benthamiana plant lines, plant growth facilities, and plasmid constructs for HPV L1 proteins, are readily available. Access to BSL-2 facilities for characterization of VLPs and pseudovirion-based neutralization assays is also confirmed. The project will build on pre-existing partnerships with laboratories at St. George’s, University of London, and Leicester University, where animal work is currently performed while SGUL BRF is not operational.   

POTENTIAL RISKS & MITIGATION PLANS
1. Gene Silencing in Stable Plant Lines: One potential risk is the gene silencing of HPV L1 protein expression in the T1 generation. This will be mitigated by employing inducible promoter systems that allow controlled expression, minimizing unintended silencing.
2. Low Recovery of VLPs: Another challenge is the low recovery rates of VLPs from plants, which can affect the vaccine’s yield. To mitigate this, we will initially optimize the purification process in transient expression systems before applying it to stable plants, ensuring scalability and sustainability.
3. Vaccine Efficacy: If preclinical models show limited immunogenicity, iterative modifications to the gene constructs and booster studies will be implemented, ensuring that the plant-derived HPV vaccine meets required efficacy standards.   

LAB ENVIRONMENT
The project will be conducted in a well-established research environment where expertise in plant molecular farming and biopharmaceutical production is extensive. The lab is equipped with advanced facilities for gene expression, plant transformation, and VLP characterization. Collaboration with international partners, including experts in LMIC-focused vaccine production, will ensure that outcomes are relevant to global health needs.

Further reading

Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)

Additional information from the supervisory team

The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.

Teh-Reljic recording

MRC LID LINKS

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